8-chromanyl carbamate esters as pesticides



United States Patent 3,548,058 S-CHROMANYL CARBAMATE ESTERS ASPESTICIDES William G. Scharpf, Rocktown, N.J., assignor to FMCCorporation, New York, N.Y., a corporation of Delaware No Drawing.Application June 9, 1966, Ser. No. 556,259, now Patent No. 3,468,913,dated Sept. 23, 1969, which is a continuation-in-part of applicationSer. No. 472,335, July 15, 1965. Divided and this application June 20,1969, Ser. No. 840,898

Int. Cl. A61k 27/00 U.S. Cl. 424-285 6 Claims ABSTRACT OF THE DISCLOSUREA new class of pesticides, useful for the control of Arthropoda andNematoda, comprises 8-chromanyl carbamate esters of the formula whereinR R R and R are each hydrogen or a lower aliphatic group; Y is hydrogenor one of a variety of groups e.g. chloro or lower alkyl; n is aninteger of 1 to 3; and X is oxygen or sulfur. Synthesis ofrepresentative compounds of this class, their use in pesticidalcompositions, and their effectiveness against insects and nematodes aredescribed.

This application is a division of application Ser. No. 556,259, filedJune 9, 1966, which is a continuationin-part of application Ser. No.472,335, filed July 15, 1965 now abandoned.

This invention relates to new chemical compounds and their preparation,to pesticidal compositions containing these new compounds, and to theuse of said compositions to control Arthropoda and Nematoda. Moreparticularly, this invention relates to certain 8-chromany1 esters ofcarbamic acids, as novel and effective pesticides.

The compounds of this invention, and their numbering system, arerepresented by the structural formula:

where R and R are each hydrogen or aliphatic groups of one to aboutthree carbon atoms including alkyl and alkenyl groups; R and R are eachhydrogen or aliphatic groups of one to about three carbon atoms,including alkyl, alkenyl, and alkynyl groups; and X is oxygen or sulfur.These compounds may be unsubstituted in the henzene ring, or may containone or more substituents Y in the benzene ring as shown, where n is aninteger of 1 to 3, which substituents Y may be the same or different andmay be lower aliphatic groups, including alkyl and alkenyl groups,halogen, haloalkyl, nitro, amino and substituted amino, cyano,alkoxycarbonyl, acyl, alkylmercapto, alkoxy, other carbamate groups, andthe like.

Compounds of the above-defined class exhibit outstanding pesticidalactivity, including effective activity against Arthropoda such asColeoptera (beetles), Hemiptera (true bugs), Homoptera (aphids), Acarina(mites), Diptera (flies and wasps), Blattaria (roaches), and Lepidoptera(moths and butterflies). In addition, several of the compounds of thisclass are particularly effective in the control of Nematoda.

Certain preferred compounds of this invention include compounds of thegeneral formula:

wherein R and R are each hydrogen or methyl, R is hydrogen or asaturated or unsaturated aliphatic hydrocarbon group of one to threecarbon atoms, and Y represents monosubstitution in the 5- or 6-positionand may be hydrogen, chlorine, or lower alkyl.

The preparation and pesticidal activity of typical compounds of thisinvention are illustrated in the following specific examples, which areprovided by way of illustration and not of limitation. All temperaturesare in de grees centigrade.

EXAMPLE 1 Preparation of 2,2-dimethyl-8-chromanyl methylcarbamzate2,2-dimethyl-8-chromanol, prepared as described by Hallet and Huls,Bull. Soc. Chim. Belg. 61, 33-43 (1952), was reacted with methylisocyanate as follows: 0.5 g. of methyl isocyanate was added to asolution of 1.0 g. of 2,2- dimethyl-8-chromanol and two drops oftriethylamine in 10 ml. of ether. The mixture was refluxed fortwenty-four hours, cooled and filtered. The white crystals were washedwith ether and with pentane to yield 0.9 g. of 2,2-dimethyl-S-chromanylmethylcarbamate, melting at 147.

Analysis.Calculated for C H NO (percent): C, 66.36; H, 7.28; N, 5.96.Found (percent): C, 66.28; H, 7.26; N, 6.21.

This compound may also be prepared by other methods. For example, manymethods of preparation of carbamic acid esters are described by Wagnerand Zook, Synthetic Organic Chemistry, chapter 23, John Wiley and Sons,New York, 1953. The intermediate 2,2-dimethyl-8-chromanol may also beprepared by alternate routes, such as that described by Hallet and Huls,op. cit., for the preparation of 2,2-dimethyl chroman.

The insecticidal and nematocidal activity of 2,2-dimethyl-S-chromanylmethylcarbamate is of a high order, as illustrated in Examples 2-4below, which demonstrate pesticidal activity under a variety ofconditions, for representative pests.

EXAMPLE 2 Insecticidal activity Insecticidal activity includingacaricidal activity was measured as follows: The compound2,2-dimethyl-8chromanyl methylcarbamate (0.5 g.) was dissolved in 40 ml.acetone and this solution was dispersed in 360 ml. of water containingone drop of Triton X400, a surfactant identified as isooctyl phenylpolyethoxy ehanol; aliquots of this solution were diluted 'with water toprovide solutions containing 1250, 312, 78, and 20 ppm. of activeingredient. Test insects and techniques were as follows: The activitiesagainst the Mexican bean beetle (Epilachna varivesiis Muls.) ,and thesouthern armyworn (Prodenia eridania [Cram.]) were evaluted by dippingthe leaves of pinto bean plants into the test solutions and infestingthe leaves with the larvae of the insects when the foliage had dried;the activity against the two-spotted spider mite (Tetranychus telarius[L.]) was evaluated on pinto bean plants whose leaves were dipped afterinfestation with adult mites; the activity against the pea aphid(Macrosiphum pisi [Harris]) was evaluated on broad bean plants whoseleaves were dipped before infestation with adult aphids; and theactivities against the milkweed bug (Oncopeltus fasciatus [Dallas]) andthe plum curculio (Conatrachelus nenuphar [Herbs-t1) were evaluated byspraying the test solutions into glass dishes containing the adultinsects. All insects in the test were maintained in a holding room at 80F. and 50% relative humidity for an exposure period of 48 hours. At thistime the number of dead and living insects were counted and the percentkill was calculated. Results presented in Table 1 are an average of tworeplicates.

TABLE 1 TABLE 3 [Nematocidal activity] 1 Root-knot index: 4=severeknotting, equivalent to untreated plants; 3=heavy knotting, but lessthan untreated plants; 2=moderate knotting; 1=slight knotting; O=noknctting, complete control.

EXAMPLE 5 Preparation and pesticidal properties of 8-chromanylmethylcarbamate [Insecticidal activity of2,2-dimethyl-8-chromany1methylcarbamate] Percent kill at- Test insect 20p.p.m. 78 p.p.rn 312 p.p.m 1,250 p.p.m. Untreated Mexican bean beetle100 100 100 100 0 Southern armyworm 10 65 70 100 0 Two-spotted spidermite 90 100 0 Pea aphid 100 100 100 100 0 Milkweed bug 100 100 100 100Plum curculio 90 100 100 5 EXAMPLE 3 Systemic insecticidal activity Thiscompound also exhibits useful systemic insecticidal activity,illustrated as follows: The roots of small lima bean plants wereexcised, and the plants were placed in Water for a period of at leastthree to four hours until they had recovered from the wilting caused byexcision of the roots. The stems of these turgid plants were theninserted into aqueous solutions of 2,2-dimethyl-8-chromanylmethylcarbamate at concentrations of 78 and 20 p.p.m. active ingredient.Twenty-four hours after the plants were placed in the test solutions theleaves were infestd with the test insects. The number of dead and livinginsects were counted forty-eight hours after infestation and the percentkill was calculated. Results presented in Table 2 below are an averageof two replicates:

TABLE 2 [Systemic insecticidal activity of 2,2-dimethyl-8-chromanylmethylcarbamate] Percent kill at The above results demonstrate excellentsystemic activity.

EXAMPLE 4 Nematocidal activity Nematode control was measured as follows:A nematode-infested soil was prepared by mixing about 1000 larvae of theroot-knot nematode (Meloidogyne incognita) into one liter of sandy-loamsoil. Into this infested soil was blended sufiicient 2,2-dimethyl-8-chromanyl methylcarbamate, formulated as a 5% dust on attapulgiteclay, to give concentrations of 100 p.p.m. and p.p.m. These mixtureswere held in the greenhouse in a moist condition for four days, thenyoung tomato plants were planted in the soil and allowed to grow forfive weeks. At this time the roots of the tomato plants were washed freeof soil and the degree of infestation was evaluated in comparison with aplant grown in nematode-infested soil which had received no chemicaltreatment. Results, shown in Table 3, represent the average of tworeplicates.

The starting material 8-hydroxychroman-4-one was prepared as follows:Catechol (450 g.) was dissolved in a hot solution of 220 g. of sodiumhydroxide in about 200 ml. of water. To this was added dropwise 360g. of3-chloropropionic acid dissolved in a solution of 230 g. of potassiumcarbonate in a minimum quantity of water. The solution was heated atreflux for ten minutes, then cooled in an ice bath and adjusted to pH 2with dilute hydrochloric acid. The aqueous solution was extracted withether. The ether extract was washed, dried over magnesium sulfate, andconcentrated, to yield 3-(o-hydroxyphenoxy) propionic acid as an oil.Approximately 900 ml. of acetic anhydride was added to this oil and theresulting solution heated at reflux overnight. Excess acetic anhydridewas distilled, and the residue was washed with water. The organic layerwas separated, and dried over magnesium sulfate to give crude3-(o-acetoxyphenoxy)propionic acid, which was added to 1.5 l. ofpolyphosphoric acid at 45 and stirred at that temperature for two hours.The reaction mixture was cooled to room temperature, diluted with water,and extracted with ether. The ether extract was washed with aqueoussodium bicarbonate, dried, and concentrated to yield solid8-hydroxychroman-4-one. The product, recrystallized from ethyl acetate,melted at 169- 170.

Analysia-Calculated for C H O (percent): C, 65.85; H, 4.91. Found(percent): C, 65.74; H, 4.85.

'Four grams of mercuric chloride was dissolved in 2.0 ml. ofconcentrated hydrochloric acid and 20 g. of washed zinc dust was added.This zinc amalgam, 5.0 g. of 8-hydroxychroman-4-one, and 30 ml. ofconcentrated hydrochloric acid were stirred at reflux for one hour. Themixture was cooled and extracted with ether, the ether layer was treatedwith sodium bicarbonate, dried over magnesium sulfate, and evaporated,to yield 5.0 g. of crude 8-chromanol, B.P. 61-64/0.07 mm.

A mixture of 2.5 g. of 8-chromanol, 1.5 g. of methyl isocyanate, 10 ml.of ether, and 2 drops of triethylamine, after standing overnight, wasdiluted with pentane and filtered. Three grams of 8-chromanylmethylcarbamate were obtained, M.P. 158. The structure of the productwas confirmed by infrared spectra.

Analysis.'Calculated for C H NO (percent): C, 63.76; H, 6.32; N, 6.76.Found (percent): C, 63.77; H, 6.41; N, 6.82.

Following the test procedures described in Example 2, S-chromanylmethylcarbamate exhibited at 1250 p.p.m. 95% kill of Mexican beanbeetles, 100% kill of southern armyworms, 95% kill of pea aphids, 100%kill of milkweed bugs, 100% kill of plum curculios, and 86% kill oftwo-spotted mites.

EXAMPLE 6 Preparation and pesticidal properties of 2,2-diethyl-8-chromany1 methylcarb amate The starting material3-ethyl-l-(o-hydroxyphenyl)-3- pentanol was prepared as described by L.I. Smith and P. M. Ruoff, J. Am. Chem. Soc, 62, 146 (1940). This product(101 g.) was dissolved in 150 ml. of glacial acetic acid and treateddropwise with 100 ml. of sulfuric acid. The mixture was heated underreflux for about two hours, then allowed to remain at room temperatureovernight. The mixture was then poured over ice and water, and extractedwith ether. The ether extractions were dried over magnesium sulfate,filtered, the ether was removed, and the resulting oil was distilledunder reduced pressure, to give 77.5 g. of 2,2-diethylchroman, B.P.5760/ 0.008

A solution composed of 150 ml. of ethyl ether and 137 ml. of a hexanesolution containing 14 g. of n-butyl lithiurn was placed in a flask andthe system purged with nitrogen. To the solution was added 40 g. of2,2-diethylchroman and the mixture was heated under reflux for twentyhours. The mixture was cooled in an ice-water bath and oxygen wasbubbled into the mixture during stirring. When absorption of oxygenceased, the mixture was acidified with cold aqueous sulfuric acid. Theether phase was separated, washed with Water, dried over magnesiumsulfate and the ether evaporated ofl. The residue was treated withdecolorizing charcoal in dry ether, and the resultant ether solutiondistilled to yield, after recovery of unreacted 2,2-diethylchroman (B.P.6573/0.1 mm), 3.8 g. of 2,2-diethy1-8-chromanol, B.P. 7 880/ 0.015 mm.

Three grams of 2,2-diethyl-8-chromanol, 3 drops of triethylamine, and1.2 g. of methyl isocyanate were reacted as in Example 5, to yield 3.0g. of 2,2-diethyl-8- chromanyl methylcarbamate, M.P. 68-70.

Analysis.--Calculated for C H NO (percent): C, 68.42; H, 8.04. Found(percent): C, 68.24; H, 7.91.

Following the test procedures of Example 2, this compound exhibited at1250 p.p.m. 100% kill of Mexican bean beetles, 100% kill of pea aphids,100% kill of milkweed bugs, and 70% kill of plum curculios.

EXAMPLE 7 Preparation and pesticidal properties of 6-ethyl-2,2-dimethy1-8-chromanyl methylcarbamate 6-ethyl-2,2-dimethy1chroman wasprepared as follows: A mixture of 122.2 g. of p-ethylphenol and 68.12 g.of isoprene was cooled to and hydrogen chloride gas passed into themixture, with external cooling to maintain the temperature at about 6.After thirty minutes, 100 ml. of glacial acetic acid was added. Hydrogenchloride addition was continued for two hours, during which time 25.4 g.hydrogen chloride was absorbed. After three days at room temperature,the mixture was distilled under reduced pressure to give6-ethyl-2,Z-dimethylchroman, B.P. 1 -126/ 9 mm., after redistillation.

Analysis.Calculated for C H O (percent): C, 82.06; H, 9.53. Found(percent): C, 82.18; H, 9.74.

6-ethyl-2,2-dimethylchroman (50.3 g.), glacial acetic acid (300 ml). andanhydrous sodium acetate (21.65 g.) were cooled in an ice bath whilebromine (42.24 g.) was added dropwise. After stirring one hour, themixture was poured into water and extracted with ether. The etherextract was dried over magnesium sulfate, filtered, and concentrated.Distillation yielded the product 8-bromo-6- ethyl-2,2-dimethylchroman,B.P. 101-5/0.15 mm.

A solution of 59.0 g. of 8-bromo-6-ethyl-2,Z-dimethylchroman in 200 ml.of ether was reacted with 14.0 g. of n-butyl-lithium, and then withoxygen, as in Example 6. Distillation gave 35 g. of6-ethyl--2,2-dimethyl-8-chroman01, B.P. -122/0.05 mm. Ten grams of6-ethyl-2,2- dimethyl-S-chromanol, 5 g. of methyl isocyanate, and 5drops of triethylamine in ethyl other were reacted as in Example 6, togive 5.5 g. of 6-ethyl-2,2-dimetl1yl-8-chromanyl methylcarbamate, M.P.114-115.

Analysis.-Calculated for C H NO (percent): C, 68.41; H, 8.04; N, 5.32.Found (percent): C, 68.24; H, 7.97; N, 5.20.

This compound was evaluated for activity against houseflies (Muscadomestica L.) as follows: 59 mg. of 6-ethyl-2,2-dimethyl-8-chromanylmethylcarbamate was dissolved in ml. of acetone which was then dilutedwith sufficient water to make 100 ml. A group of 3040 houseflies,immobilized under carbon dioxide, was placed on a moist filter paperheld on a Buchner funnel attached to a vacuum source. Twenty-five ml. ofthe test solution was poured over the immobilized flies, this beingsuflicient volume that all were completely immersed. Vacuum was thenapplied to remove the test solution and the flies were transferred toholding cages lined with absorbent paper. Mortality counts madetwenty-four hours after treatment showed 100% kill of houseflies.

EXAMPLE 8 Preparation and pesticidal properties of2,2,5-trimethyl-S-chromanyl methylcarbamate The intermediate5,6,7,8-tetrahydro-2,2-dimethylchroman-S-one was prepared by the methodof V. I. Gunar and S. I. Zavyalov, Izvest, Akad. Nauk. SSSR 1960, 937;CA. 54, 24700f (1960). To a solution of 50 g. of this compound in 100m1. of ether was added, under nitrogen atmosphere, 130 ml. of a 3 molarsolution of methylmagnesium bromide solution in ethyl ether. Whenaddition was complete, the mixture was heated under reflux for twohours, 200 ml. of cold 10% sulfuric acid was added, and reflux continuedfor one hour. The ether layer was separated, dried, and concentrated toyield crude 7,8-dihydro-2,2,5-trimethylchroman. This crude product wasadded to g. of chloranil in 600 ml. of benzene and the mixture heatedunder reflux for 16 hours. The reaction mixture was cooled and filtered.The filtrate was washed, dried, and concentrated to yield a brown oil,which was purified by chromatographing through an alumina column usingpentane as the eluant, to give purified 2,2,5-trimethylchroman, B.P.60-61/0.1 mm.

2,2,5-trimethylchroman (16 g.) was reacted with n-butyllithium (6.4 g.),and the lithiated product treated with oxygen, according to theprocedure described in Example 6, to give 1.5 g. of2,2,5-trimethyl-8-chromanol. This product was reacted with methylisocyanate as in Example 6, to yield 1.2 g. of2,2,5-trimethyl-8-chromanyl methylcarbamate, M.P. 132.5133.5 onrecrystallization from hexane.

Analysis.-Calculated for C H NO (percent): C, 67.44; H, 7.68; N, 5.62.Found (percent): C, 67.16; H, 7.58; N, 5.55.

This compound was tested for insecticidal activity by the procedure setforth in Example 2. At 1250 ppm, 80% kill of Mexican bean beetles, killof milkweed bugs, 100% kill of plum curculios, and 100% kill oftwospotted mites was obtained.

EXAMPLE 9 Preparation and pesticidal properties of 5-chloro-2,2-

dimethyl-8-chromanyl inethylcarbamate 2,2dimethyl-8-chromanol waschlorinated as follows: To a stirred solution of 18 g. of2,2-dimethyl-8-chromanol in 50 ml. of chloroform was added dropwise 13.5g. of sulfuryl chloride. Gas evolution began immediately. The mixturewas stirred overnight at room temperature. The

solvent was removed by evaporation and the residue distilled through aspinning band column to yield 2.2 g. of-chloro-2,2-dimethyl-8-chromanol, B.P. 132145 0.05

Analysis.--Calculated for C H ClO (percent): C, 62.11; H, 6.15. Found(percent): C, 61.66; H, 6.30.

5-chloro-2,2-dimethyl-8-chromanol (8.5 g.) was reacted with 2.4 g. ofmethyl isocyanate by the procedure described in Example 1 to give 5.3 g.of 5-chloro-2,2-dimethyl-S-chromanyl methylcarbamate, M.P. 128-129".

Analysis-Calculated for C H ClNO (percent): C, 57.88; H, 5.98; N, 5.19.Found (percent): C, 57.97; H, 5.83; N, 5.40.

Following the procedure described in Example 2, this compound gave, at1250 p.p.m., 90% kill of Mexican bean beetles, 80% kill of southernarmyworms, 100% kill of pea aphids, 100% kill of milkweed bugs, and 100%kill of plum curculios.

EXAMPLE Preparation and pesticidal properties of 2,2-dipropyl-8-chromanyl methylcarbamate Following the procedure set forth in Example6, propylmagnesium bromide was reacted with chroman-2-one, to form1-(o-hydroxyphenyl)-3-propyl-3-hexanol, M.P. 64- 66". By action ofacetic acid in the presence of sulfuric acid, this product was cyclizedto give 2,2-dipropylchroman, B.P. 7l-74/0.007 mm., which was convertedby lithiation and oxidation, also as in Example 6, to 2,2-dipropyl-8-chromanol, B.P. 95/0.25 mm. Reaction of this chromanol withmethyl isocyanate according to the procedure of Example 6 gave2,2-dipropyl-8-chromanyl methylcarbamate, M.P. 99-100.

Analysis.-Calculated for C H NO (percent): C, 70.07; H, 8.65; N, 4.81.Found (percent): C, 70.36; H, 8.78; N, 4.83.

Following the procedures of Example 2, this compound gave 100% kill ofMexican bean beetles, at 1250 ppm.

EXAMPLE 1 1 Preparation and pesticidal properties of 6-sec-butyl-2,2-dimethyl-8-chromanyl methylcarbamate To a stirred solution of 500 g. ofisoprene and 200 g. of 4-sec-butylphenol in 1500 ml. of glacial aceticacid was added 30 g. of anhydrous zinc chloride and 30 drops ofconcentrated sulfuric acid. After one hour, an additional drops ofsulfuric acid was added, followed by another 20 drops one hour later.Stirring at room temperature was continued for four days. The mixturewas then poured into one liter of water, the organic layer was separatedand washed, dried, and concentrated on an evaporator. Distillation ofthe residue over the range of 123-203/ 10 mm. gave 134 g. of crude6-sec-butyl-2,2rdimethylchroman, which on fractional redistillationboiled at 141- 144/ 13 mm.

Analysis.Calculated for C H O (percent): C, 82.52; H, 10.16. Found(percent): C, 82.67; H, 10.02.

This product was hydroxylated by treatment with n-butyllithium and withoxygen, as in Example 6, to give 6-sec-butyl-2,2-dimethyl-8-chromanol,B.P. 91-95 0.2 mm. This chromanol was reacted with methyl isocyanate bythe procedure of Example 1 to give 6-sec-butyl-2,2-dimethyl-S-chromanylmethylcarbamate, M.P. 169170.

Analysis.-Calculated for C H NO (percent): C, 70.07; H, 8.65; N, 4.81.Found (percent): C, 70.21; H, 8.50; N, 5.03.

Following the test procedure of Example 2, this compound at 1250 ppm.gave 92% kill of housefiies.

EXAMPLE 12 Preparation and pesticidal properties of 2,2,7-trimethyl-8-chromanyl methylcarbamate 2,2,7-trimethylchroman was prepared asfollows: A dry suspension of sodium hydride (88.8 g.) in 400 ml. benzenewas purged with nitrogen and to it was slowly added 209.1 g. of m-cresolin 500 ml. benzene. The mixture was stirred at room temperature for twohours. The suspension of sodium salt was cooled to 5 and to it was addeddropwise 219.7 g. of 1-chloro-3-methyl-2-butene while the temperaturewas maintained at about 5. After two hours at this temperature, stirringwas continued three days without external cooling. The mixture was thenheated under reflux for one hour, cooled to room temperature, andacidified with dilute sulfuric acid. The organic layer was separated andthe benzene removed by evaporation, to yield 354.5 g. of dark red oil.To this crude mixture of 2-(3-methyl-2-buten-1-yl)-3- and-5-methylphenols was added dropwise 7 ml. of concentrated sulfuric acid.The temperature rapidly increased to 100, then began to decrease. Atroom temperature, 500 ml. of benzene was added. The benzene solution waswashed with dilute sodium bicarbonate solution and with water, dried,and the benzene was evaporated. The residue was distilled under reducedpressure to give 152.1 g. of a mixture of 2,2,5- and2,2,7-trimethylchromans, B.P. 99-124/l5 mm. This mixture was separatedusing a gas chromatograph. The desired 2,2,7-trimethylchroman wasidentified by nuclear magnetic resonance.

2,2,7-trimethylchroman was treated with n-butyllithium and oxygen as inExample 6, to give 2,2,7-trimethyl-8- chromanol, B.P. 79/0.03 mm. Thischromanol was reacted with methyl isocyanate as in Example 1, to give2,2,7-trimethyl 8 chromanyl methylcarbamate, M.P. 1-15116 from hexane.

AnaIysis.--Calculated for =C H NO (percent): C, 67.44; H, 7.68. Found(percent): C, 67.59; H, 7.44.

Following the test procedure of Example 2, this product exhibited at1250 ppm. 95% kill of milkweed bugs and 45% kill of plum curculios.

EXAMPLE 13 Preparation and pesticidal properties of 2,2-dimethyl-8-chromanyl dimethylcarbamate 2,2-dimethyl-8-chromanol (26.7 g.), preparedas in Example 1, was added dropwise at room temperature to a solution ofsodium methoxide, prepared by dissolving 3.45 g. of sodium metal in 50ml. of methanol. The mixture was heated at 50 for one hour and themethanol removed by distillation under reduced pressure. The stickysolid which remained was triturated with hexane and filtered to give awhite powder. To a solution of 13.5 g. of this sodium salt in ml. ofdioxane was added dropwise 7.5 g. of dimethylcarbamoyl chloride. Afterthe exothermic reaction subsided, the slurry was heated at 75 for twohours. The slurry was concentrated under reduced pressure and theresidue diluted with 100 ml. of ether. The ether solution was washedwith water, dried, and distilled to yield 7.1 g. of2,2-dimethy1-8-chromanyl dimethylcarbamate, B.P. 101102/0.01 mm.

Analysis.Calculated for C H NO (percent): C, 67.45; H, 7.68; N, 5.62.Found (percent): C, 67.57; H, 7.50; N, 5.90.

When tested at 1250 ppm, by the procedure of Example 2, this compoundgave 'kill of Mexican bean beetles, kill of pea aphids, 100% kill ofmilkweed bugs, and 100% kill of plum curculios.

EXAMPLE 14 Preparation and pesticidal properties of 2,2-dimethyl-8-chromanyl propylcarbamate To a solution of 11.75 g. of2,2-dimethyl-8-chromanol and 0.2 g. of 1,4-diazabicyclo(2.2.2)octane in75 ml. of ethyl ether was added dropwise with stirring, 6.0 g. of propylisocyanate. The mixture was stirred at room temperature overnight. Theether and excess methyl isocyanate was removed by distillation and theresidue diluted with petroleum ether. The solid was collected to obtain7.0 g. of 2,2-dimethyl-8-chromanyl propylcarbamate, M.P. 71-72 (fromhexane).

When tested by the procedure of 'Example 2, this compound at 1250 p.p.m.gave 100% kill of Mexican bean beetles, 100% kill of pea aphids, 100%kill of milkweed bugs, and 47% of two-spotted mites.

EXAMPLE 15 Preparation and pesticidal properties of 2,2-dimethyl-8-chromanyl allylcarbamate 2,2-dimethyl-'8-chromanol (16.2 g.) was reactedwith 6.0 g. of allyl isocyanate in 50 ml. of benzene, according to theprocedure of Example 14, to give, after recrystallization from hexane,8.5 g. of 2,2-dimethyl-8-chromanyl allylcarbamate, M.P. 70-71.

Analysis.-Calculated for C H NO (percent): C, 68.94; H, 7.33; N, 5.36.Found (percent): C, 68.89; H, 7.04; N, 5.47.

When tested according to the procedure of Example 2, this compound at1250 p.p.m. gave 100% kill of Mexican bean bettles, 100% kill ofsouthern armyworms, 100% kill of pea aphids, 100% kill of milkweed bugs,90% kill of plum curculios, and 87% of two-spotted mites.

EXAMPLE 16 Preparation and pesticidal properties of 2,2-dimethyl-8-chromanyl propargylcarbamate To a solution of 25 g. of2,2-dimethyl-8-chromanol in 100 ml. of benzene at was added 11 ml. ofliquid phosgene. While the temperature was maintained at 4-7", 14.2 g.of triethylamine was added dropwise. The mixture was stirred for onehour at 5, then for two hours at 25. The slurry was diluted with 150 ml.cold water. The benzene layer was separated, dried, and concentrated toleave 32.5 g. of yellow oily 2,2-dimethyl-8-chrornanyl chloroformatewhich was used without further purification. A solution of 16.2 g. ofthis crude chloroformate in 50 ml. benzene was added dropwise to astirred solution of 3.7 g. propargylamine and 6.8 g. triethylamine in 25ml. benzene. The slurry Was stirred for three hours at 5060, then cooledto 20 and filtered. The filtrate was washed with cold water, dried, andconcentrated by evaporation. The residual oil was diluted with hexaneand the white solid isolated by filtration to yield 8.0 g.2,2-dimethyl-8-chromanyl propargylcarbamate, which on recrystallizationfrom hexane gave 7.0 g. of platelets, M.P. 95-955".

Analysis.Calculated for CH17NO3 (percent): C, 68.48; H, 6.61; N, 5.40.Found (percent): C, 69.68; H, 6.74; N, 5.48.

When tested according to the method of Example 2,

this compound at 1250 ppm. gave 100% kill of Mexican bean bettles, 100%kill of southern armyworms, 100% kill of pea aphids, 100% kill ofmilkweed bugs, and 45% kill of plum curculios.

Other compounds of this class of insecticidal chromanyl carbamates maybeprepared by adaptation of the synthetic procedures illustrated hereinand by related procedures. The intermediate 8-chromanols may beconverted to the carbamates by standard procedures, such as reactionwith the appropriate isocyanate; or with phosgene to form thechloroformate or the bis(carbonate), which is then reacted with theappropriate amine to form the carbamate; or alternatively by thetransesterification of phenyl N- monoor N,N-disubstituted carbamateswith the appropriate 8-chromanol. The intermediate 8-chromanols, eitherunsubstituted or substituted in the 2-, 5-, 6-, or 7-position, may beprepared by a variety of methods, the desired product, of course,determining the specific starting material and methods to be employed.For example, the desired chroman, unsubstituted or substituted, may belithiated as described by Ballet and Huls, (op. cit.), to give the8-lithium compound which is oxidized and then hydrolyzed to the8-chromanol. Bromination of the chromans also proceeds to the8-bromocompound, which may be converted to the 8-hydroxycompound byseveral processes, such as (a) hydrolysis with alkali in a high-boilingprotonic solvent such as ethylene glycol in the presence of a coppercatalyst; (b) lithiation of the 8-bromocompound, either directly withmetallic lithium or by exchange with an alkyllithium such asn-butyllithium, followed by oxygenation and hydrolysis; (0) conversionto the corresponding Grignard reagent, and oxygenation of the Grignard,as described by Porter and Steel, J. Am. Chem. Soc. 42, 2650 (1920).

Nitration of chromans also gives the 8-nitro compound which is readilyreduced to the 8-amino compound. Diazotization of 8-aminochromans andsubsequent hydrolysis of the diazonium salt gives the desired 8-chromanol. Other procedures may be used, such as the hydrolysis of8-methoxychromans by an ether-cleaving acid such as hydroiodic acid, togive the corresponding 8-chromanols.

The appropriately substituted chromans may be prepared by a variety ofprocedures, starting with intermediates in which either both rings arepresent, or only the aromatic ring is present, or no aromatic ring ispresent. Thus, a hydroxyphenylalkanol is formed by reaction of anappropriately substituted chroman-Z-one with an alkyl Grignard reagent(Smith and Ruotf, J. Am. Chem. Soc. 62, (1940)); cyclization of thisalkanol in the presence of acid gives a 2,2-dialkylchroman in which thealkyl group corresponds to that of the Grignard reagent. Reaction of theappropriately substituted phenol with isoprene in the presence of acidcatalysts, such as zinc chloride or acetic acid-sulfuric acid mixtures,gives the corresponding substituted 2,2-dimethylchroman, as described byClaisen, German Pat. 374,142; m-substituted phenols give mixtures of the5- and 7-substituted 2,2- dimethylchromans. Similarly, the aluminum saltof the appropriate substituted phenol reacts with isoprene to give thecorresponding substituted 2,2-dimethylchroman (British Pat. 906,483).Other procedures may also be adapted to the synthesis of this class ofcompounds, such as that exemplified by condensation of the sodium saltof cyclohexane-1,3-dione with 1-chloro-3-methyl-2- butene to give2-(3-methyl-2-buten-1-yl)-.cyclohexane- 1,3-dione, which on treatmentwith acid cyclizes to 5,6,7,8-tetrahydro 2,2 dimethyl-chroman-S-one;this chromanone reacts With an alkyl Grignard reagent to give anintermediate 5-chromanol which in the presence of acid, such as sulfuricacid, dehydrates and aromatizes to give a 5-alkyl-2,Z-dimethyhchroman.

The foregoing reactions are of course not limited to the specificcompounds mentioned. Through the use of the appropriate startingmaterials and reagents, 8- chromanyl carbamates with the desiredsubstituent or substituents in the aromatic and/or heterocyclic ring maybe obtained.

The compounds of this invention are toxic to a variety of crop andhousehold pests, in addition to the typical pests exemplified above.Like most agricultural chemicals, they are not usually applied fullstrength, but are generally incorporated with the adjuvants and carriersnormally employed for facilitating dispersion of active ingredients foragricultural chemical applications, recognizing the accepted fact thatthe formulation and mode of application may alfect the activity of amaterial. The toxicants of this invention may be applied as sprays,dusts, or granules. They may be formulated as granules of large particlesize, as powdery dusts, as wettable powders, as emulsifiableconcentrates, as. solutions, or as any of several other known types offormulations, depending on the desired mode of application.

Wettable powders are in the form of finely divided particles whichdisperse readily in water or other dispersant. These compositionsnormally contain from 80% toxicant and the rest inert material whichincludes dispersing agents, emulsifying agents, and wetting agents. Thepowder may be applied to the soil as a dry dust or preferably as asuspension in water. Typical carriers include fullers earth, kaolinclays, silicas, and other highly absorbent, readily wet, inorganicdiluents. Typical wetting, dispersing, or emulsifying agents used inagricultural formulations include, for example, the alkyl and alkylarylsulfonates and sulfates and their sodium salts; alkylamide sulfonates,including fatty methyl taurides; alkylaryl polyether alcohols, sulfatedhigher alcohols, and polyvinyl alcohols; polyethylene oxides; sulfonatedanimal and vegetable oils; sulfonated petroleum oils; fatty acid estersof polyhydric alcohols and the ethylene oxide addition products of suchesters; and the addition products of long chain mercaptans and ethyleneoxide. Many other types of useful surface active agents are available incommerce. The surface active agent, when used, normally comprises fromone percent to fifteen percent by weight of the pesticidal composition.A typical formulation for use herein is as follows: 25.0% of the desired8-chromanyl carbamate, 72.0% attapulgite clay, 1.5% sodiumlignosulfonate, and 1.5% sodium alkylnaphthalene sulfonate.

Dusts are freely flowing admixtures of the active ingredient with finelydivided solids such as talc, natural clays, kieselguhr, pyrophyllite,chalk, diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulfur, lime, flours, and other organic and inorganic solidswhich act as dispersants and carriers for the toxicant. These finelydivided solids have an average particle size of less than about fiftymicrons. A typical dust formulation useful herein contains 5.0% of the8-chromanyl carbamate and 95.0% talc.

Useful liquid concentrates include the emulsifiable concentrates, whichare homogeneous liquid or paste compositions which are readily dispersedin water or other dispersant, and may consist entirely of the toxicantwith a liquid or solid emplsifying agent, or may also contain a liquidcarrier, such as xylene, heavy aromatic naphthas, isophorone, and othernon-volatile organic solvents. For application these concentrates aredispersed in water or other liquid carrier, and normally applied as aspray to the area to be treated. The percentages by weight of thetoxicant may vary according to the manner in which the composition is tobe applied, but in general comprises 0.5 to 95% of active ingredient byweight of the pesticidal composition.

Other useful formulations for insecticidal or nematocidal applicationsinclude simple solutions of the active ingredient in a dispersant inwhich it is completely soluble at the desired concentration, such asacetone, alkylated naphthalenes, xylene, or other organic solvents.Granular formulations, wherein the toxicant is carried on relativelycoarse particles, are of particular utility for aerial distribution orfor penetration of cover crop canopy. Baits, prepared by mixing solid orliquid concentrates of the toxicant with a suitable food, such as amixture of cornmeal and sugar, are useful formulations for control ofinsect pests. Pressurized sprays, typically aerosols wherein the activeingredient is dispersed in finely divided form as a result ofvaporization of a low-boiling dispersant solvent carrier, such as theFreons, may also be used. All of these techniques for formulating andapplying the active ingredient are well known in the art.

The pesticidal compositions may be formulated and applied with otheractive ingredients, including other nematocides, insecticides,fungicides, bactericides, plane growth regulators, fertilizers, etc. Inapplying the chemical an effective amount and concentration of the 8-chromanyl carbamate is of course employed.

It is apparent that various modifications may be made in the formulationand application of the novel compounds of this invention, withoutdeparting from the inventive concepts herein, as defined in thefollowing claims:

I claim:

1. A pesticidal composition comprising an extender and an effectiveamount of a compound of the formula:

wherein R and R are each selected from the group consisting of hydrogenand alkyl and alkenyl groups of one to about three carbon atoms; R and Rare each selected from the group consisting of hydrogen and alkyl,alkenyl, and alkynyl groups, each containing one to about three carbonatoms; Y represents one or more substituents selected from the groupconsisting of hydrogen, lower alkyl and lower alkenyl groups, halogen,nitro, amino, and cyano groups; n is an integer of l to 3; and X isselected from the group consisting of oxygen and sulfur.

2. A pesticidal composition comprising an extender and an effectiveamount of a compound of the formula:

wherein R and R are each selected from the group consisting of hydrogenand methyl; R is selected from the group consisting of hydrogen andalkyl, alkenyl, and alkynyl radicals, each containing one to threecarbon atoms; and Y represents monosubstitution in the 5- or 6- positionand is selected from the group consisting of hydrogen, chlorine, andlower alkyl.

3. A pesticidal composition comprising an extender and an effectiveamount of the compound 2,2-dimethyl- 8-chromanyl methylcarbamate.

4. The method of controlling Arthropoda and Nematoda which comprisessubjecting them to an effective dose of a compound of the formula:

wherein R and R are each selected from the group consisting of hydrogenand alkyl and alkenyl groups of one to about three carbon atoms; R and Rare each selected from the group consisting of hydrogen and alkyl,alkenyl, and alkynyl groups, each containing one to about three carbonatoms; Y represents one or more substituents selected from the groupconsisting of hydrogen, lower alkyl and lower alkenyl groups, halogen,nitro, amino, and cyano groups; n is an integer of 1 to 3; and X isselected from the group consisting of oxygen and sulfur.

5. The method of controlling Arthropoda and Nematoda which comprisessubjecting them to an effective dose of a compound of the formula:

wherein R and R are each selected from the group consisting of hydrogenand methyl; R is selected from the group consisting of hydrogen andalkyl, alkenyl, and alkynyl radicals, each containing one to threecarbon References Cited UNITED STATES PATENTS 2,939,851 6/1960 Orchin260482 3,084,182 4/1963 McElroy 260482 3,122,551 2/1964 Zaugg et a1260345.2 3,344,170 9/1967 Strycker 260482 atoms; and Y representsmonosubstitution in the S- or 15 STANLEY J. FRIEDMAN, Primary Examiner

